EXPRESSION OF FUNCTIONAL C-KIT RECEPTORS RESCUES THE GENETIC-DEFECT OF W MUTANT MAST-CELLS

被引:34
作者
ALEXANDER, WS [1 ]
LYMAN, SD [1 ]
WAGNER, EF [1 ]
机构
[1] IMMUNEX CORP,SEATTLE,WA 98101
关键词
C-KIT RECEPTOR; MAST CELL GROWTH FACTOR; RETROVIRAL GENE TRANSFER; STEEL FACTOR; W LOCUS;
D O I
10.1002/j.1460-2075.1991.tb04936.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Loss-of-function mutations in the gene for the c-kit tyrosine kinase receptor are strongly implicated in the developmental abnormalities of W mutant mice. To dissect further the relationship between kit and the W phenotype, retroviruses carrying the normal murine c-kit gene were constructed. In infected cells, the level of c-kit expression from these vectors varied markedly with different promoter elements, the 5' viral LTR proving to be the most effective. When introduced into cells which normally do not express c-kit, ectopic kit receptors transduced a ligand (Steel factor)-dependent proliferative signal in IL-3-dependent DA-1 myeloid cells and induced transformation in fibroblasts. Primary mutant mast cells were used to examine the effects of reconstituting functional kit expression in cells affected by W mutations. Exogenous c-kit expression rescued the defective proliferative response to Steel factor of cells from both W/W(v) and W/W mutant mice. Moreover, functional kit expression also restored the capacity of W/W(v) mast cells to survive and differentiate in vivo. These results imply that defective c-kit receptor function is sufficient to generate the W mutant phenotype.
引用
收藏
页码:3683 / 3691
页数:9
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